AgBioResearch

For generations, apple and pear growers in the United States have been dependent on a small number of antibiotics applied during bloom time to protect trees from infection by a destructive and costly bacterial disease known as fire blight. Despite effectiveness in the field, however, antibiotic use in plant agriculture has become part of the discussion of increasing human drug resistance concerns.

In fact, a new regulation will eliminate the use of antibiotics in organic apple and pear production beginning this fall. The controversial decision was made by the National Organic Standards Board (NOSB) after urgings from consumer and environmental advocates, who cited mounting evidence that antibiotic resistance is a serious health threat. The ruling also marks the end of antibiotic use in all organic food production, including livestock.

David Epstein, a former Michigan State University (MSU) entomologist who has worked closely with the fruit industry and is now with the U.S. Department of Agriculture (USDA), said the recent NOSB decision may dampen fruit grower interest in organic production.

“I’ve already heard from a number of organic growers in Michigan who told me that they will stop producing organically if they can’t protect their trees [from fire blight] because of a lack of effective organic treatment options,” Epstein said. “Antibiotic use in tree fruit orchards is relatively minor, occurring early in the season and only when necessary, not prophylactically. Many growers believe that antibiotic use in apple and pear production is generally misunderstood.”

The new regulation has unquestionably added pressure to find workable fire blight control alternatives, not just for the organic industry but for conventional fruit growers as well.

The problem at hand: fire blight

Fire blight is caused by the bacterial pathogen Erwinia amylovora (E. amylovora), which infects the flowers of blooming apple and pear trees. It can quickly spread into the branches and ultimately kill the tree and sometimes entire orchard blocks. Signs of infection include cankers, which ooze sticky amber-colored droplets, each containing millions of bacterial cells onto the shoots and leaves, and branches of dry, brown, curled leaves in the shape of a shepherd’s crook. It is a serious problem worldwide, particularly in wet, humid climates such as Michigan, where a fire blight epidemic in 2000 killed 400,000 apple trees and caused $42 million in damages.

MSU AgBioResearch plant pathologist and Extension specialist George Sundin, who has been studying fire blight for 12 years, has guided the Michigan fruit industry on treatment options. He said well-timed sprays of antibiotics are the most effective and economical means of preventing the bacterial disease. Their use in plant agriculture is regulated by the U.S. Environmental Protection Agency (EPA), which requires growers to keep detailed spray records. Despite governmental regulation, the issue is controversial and complex, and consequently ripe for public speculation and misinformation.

“There is no question that some people are potentially not happy about the use of antibiotics in plant agriculture,” Sundin said. “But that’s in large part because they really don’t know much about it. For example, growers apply antibiotics only when disease models indicate a high likelihood of infection. Otherwise, they don’t spray because it would be economically unwise.”

In general, the industry contends that the use of antibiotics in plant agriculture — which amounts to 0.5 percent of all antibiotic use — is extremely low and, therefore, not a significant factor in the antibiotic resistance equation. The bulk of agricultural antibiotic use is in livestock production. Sundin, who spoke last fall at the National Institute of Animal Agriculture symposium “Bridging the Gap between Animal Health and Human Medicine,” explained that the use of antibiotics in plants is markedly different from their use in humans or in animals.

“First, there are a lot of similar bacteria that colonize animals and people,” Sundin explained. “There are even pathogens that occur in animals that can be passed on to people. Also, some animals are given similar antibiotics that people are prescribed, which I believe increases the potential for the transfer of medically important antibiotic resistance genes that can find their way into the human bacterial population.”

The fact that bacteria found in plants are typically different from those in humans and animals decreases the potential impact on resistance in human pathogens.

“Overall in the plant system, the amount and kinds of resistance genes are much lower than in animals or people,” Sundin explained. “And critical human antibiotics are not used in the plant systems. So, first, I think that helps us because we don’t have these resistance genes to begin with. Second, the bacteria are quite different for the most part. You do find E. coli associated with plants and Salmonella with incidents of food poisoning, but their levels of association are relatively low. Those bacteria can contaminate plants, but they generally don’t grow on them well.”

The most effective treatment options

It wasn’t long after antibiotics began curing victims of fatal diseases that plant pathologists recognized the potential for treatment of plant diseases. During the 1950s, some 40 antibiotics of bacterial or fungal origin were screened for plant disease control. Low toxicity to the plant and effectiveness in small doses made them appealing to farmers, who had been primarily reliant on metal-based bactericides.

Today, apple and pear growers in the United States primarily utilize three antibiotics — two of which are used in human medicine — for fire blight control:

1. Streptomycin – Discovered in 1944, it was primarily used in human medicine for the treatment of tuberculosis. Because of severe side effects, however, its current use in humans is minimal. It has been used for crop protection in the United States since 1955 and today is the most used antibiotic in plant agriculture.
2. Oxytetracycline – Discovered in 1950, it is a broad-spectrum antibiotic used in human medicine to treat some bacterial infections of the eye, genitals and chest, to name a few. It is also used to treat some diseases and infection in cattle, poultry and fish (aquaculture). Its use in plant agriculture started in the 1970s after reports of streptomycin-resistant E. amylovora in the western United States.
3. Kasugamycin – Discovered in 1965 in the soil of Japan and found to inhibit growth of a fungus causing rice blast disease, this naturally occurring antibiotic used only in agriculture requires a special use permit in the United States from the EPA. It has been used in Michigan for the past five years. It is registered for agricultural use in Canada. It has no human or animal medical use.

Plant-grade antibiotics are typically formulated as powders consisting of 17 to 20 percent active ingredient. The powders are dissolved or suspended in water and applied as a fine mist to the tree canopies. Because they are relatively expensive, the antibiotics are primarily used on high-value fruit.

Both streptomycin and oxytetracycline have been assigned the lowest toxicity rating by the EPA, and neither has shown carcinogenic or mutagenic activities. Those who handle the antibiotics must wear long sleeves, long pants and waterproof gloves. A mask is required for streptomycin application and protective eyewear for oxytetracycline application.

Resistance of plant pathogens to oxytetracycline is rare, but the emergence of streptomycin-resistant strains has impeded the control of several important plant diseases. A fraction of streptomycin resistance genes in plant-associated bacteria are similar to those isolated from humans, animals and soil. The most common vehicles of streptomycin resistance genes in human and plant pathogens are genetically distinct, however.

“The antibiotics streptomycin and oxytetracycline are older, so the resistance genes for those were spread around the world long ago, probably in the 1950s or 1960s, when they were used in humans,” Sundin said. “Plant pathogens have picked up resistance to streptomycin and have picked up resistance genes just because they’re everywhere now. And in oxytetracycline, there’s really not much evidence for resistance in plant pathogens.”

Two recent studies from the University of Wisconsin examined the use of streptomycin in apple orchards and the corresponding impact on resistance. The research projects, one of which examined the plant leaves while the other looked at the soil, both concluded there were “factors other than streptomycin exposure” that drove the genetic structure of the bacterial community. Studies on Kasugamycin use in Michigan orchards have had similar findings.

“Basically, what we found in our study in Michigan is very similar to what the University of Wisconsin studies show — that the types of resistance and the amount were similar whether Kasugamyin had been sprayed or not,” Sundin said.

The antibiotic application process in crop agriculture is often scrutinized because the treatment is sprayed in the field before infection actually occurs. A protective barrier must be formed on the plant’s surface to prevent infection of the tree.

“Unlike what happens when we take an antibiotic pill and it circulates throughout our blood system, you can’t spray a plant and have that same effect — the drug going throughout its system,” Sundin said. “Instead, you have to spray the antibiotic on the flower surface while the tree is in bloom. This provides a protective barrier so that, when the bacteria land on the flower, they are killed.”

Searching for workable alternatives

A team of Michigan State University (MSU) researchers led by Sundin is examining alternative organic methods for controlling fire blight. The three-year project is funded by a $464,000 grant from the U.S. Department of Agriculture (USDA). Researchers will begin a renewed investigation into several biological controls, including a yeast product called Blossom Protect and bactericides made from copper solutions.

Blossom Protect, a biological pesticide, works by introducing highly competitive microorganisms onto the fruit blossom, which block the pathogen from colonizing. It contains live strains of yeast that are mixed with a citric acid buffer. The citric acid lowers the pH in the blossom, inhibiting the growth of the fire blight bacteria when they enter the blossom.

“We’ve had inconsistent results from Blossom Protect in the past, but our goal now is to study it in greater detail,” Sundin said. “We need to better understand the mechanism of how it colonizes the flowers and controls fire blight, how it competes with the pathogen under different temperature and wetness regimes, and when the right time is to apply it.”

Copper bactericides pose trade-offs for growers. Though they’re effective at controlling fire blight, the sprays can cause blemishes that decrease market value of the fruit. Another potential benefit is that researchers have no reason to believe that copper poses a risk of resistance development.

By systematically looking at these options, Sundin said he is hopeful that he will be able to provide growers with the tools they need to protect their crops.

“Understanding how to optimize the use of organically certified materials for fire blight control is really important,” he said. “These materials may seem weaker than streptomycin simply because we’re not using them correctly.”

While the USDA-funded project will likely have results conventional growers can benefit from, the researchers say helping organic growers, especially in Michigan, is of utmost importance. MSU AgBioResearch entomologist Matt Grieshop will assist in the farm experiments and outreach objectives.

“Organic growers are in desperate need of antibiotic alternatives if they are to maintain their organic certification,” Grieshop said. “Without effective, organically compliant fire blight management tactics, organic apple production will be greatly reduced.”

Having the right techniques to ensure healthy crops is one of the best ways to prevent the decline of organic production.

“Michigan gets a lot of disease pressure because of our climate,” Sundin said. “We need good management tools. That’s something we have for conventional apples but not yet for organics. Organic produce is becoming more and more important to Michigan consumers. There’s no reason for them to have to get their apples from Washington if we can grow them here.”

The research project will conclude in summer 2016. Sundin said he plans to upload videos to http://www.youtube.com/user/treefruitpathology as progress is made.

In the meantime, Epstein said he has been asked by colleagues at the USDA National Organic Program to help expedite registration of some of these newer materials for organic use in light of the NOSB regulation. He said speeding up the process may bring little comfort to growers faced with losing tried and tested control materials for reasons they believe are unscientifically substantiated.

“For a grower who perceives the elimination of materials as being based on perception rather than reality, it’s certainly a bitter pill to swallow,” he said.

Antibiotic Resistance brochure